IE900798L - Use of tetrahydronaphthylamines - Google Patents

Use of tetrahydronaphthylamines

Info

Publication number
IE900798L
IE900798L IE900798A IE79890A IE900798L IE 900798 L IE900798 L IE 900798L IE 900798 A IE900798 A IE 900798A IE 79890 A IE79890 A IE 79890A IE 900798 L IE900798 L IE 900798L
Authority
IE
Ireland
Prior art keywords
compound
cis
tetrahydro
use according
naphthalenamine
Prior art date
Application number
IE900798A
Other versions
IE81047B1 (en
Inventor
Billie Kenneth Koe
Original Assignee
Pfizer
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=23244506&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=IE900798(L) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Pfizer filed Critical Pfizer
Publication of IE900798L publication Critical patent/IE900798L/en
Publication of IE81047B1 publication Critical patent/IE81047B1/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/13Amines
    • A61K31/135Amines having aromatic rings, e.g. ketamine, nortriptyline
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/18Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/06Immunosuppressants, e.g. drugs for graft rejection

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Pain & Pain Management (AREA)
  • Transplantation (AREA)
  • Rheumatology (AREA)
  • Psychiatry (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

4-Phenyl-1,2,3,4-tetrahydro-1-naphthalenamine derivatives have been found useful for the treatment of pyschosis, inflammation, stroke and as imnunosunpressants.

Description

—! - 0 i U 4 / 9 G 0 7 9 g 6 USE OF 4-PHENYL-1,2,3,4-TETRAHYDRO-1-NAPHTHALENAMINE DERIVATIVES IN THE TREATMENT OF PSYCHOSIS, INFLAMHATION, STROKE AND AS IMMUNOSUPPRESSANTS The present invention relates to the use of 5 4-phenyl-l,2,3,4-tetrahydro-l-naphthalenamine derivatives in the treatment of psychosis, inflammation, stroke and as immunosuppressants.
United States Patent No. 4,536,518 discloses cis-4-phenyl-l,2,3,4 -tetrahydro- 1 - naphthalenamine 10 derivatives useful as antidepressants.
United States Patent No. 4,556,676 discloses trans-4-phenyl-l,2,3,4-tetrahydro-l-napthalenamine derivatives useful as antidepressants.
It has now been discovered that the compounds 15 disclosed in the aforementioned United Stares patents have sigma receptor binding activity and are therefore useful in the treatment of psychosis, inflammation and as immunosuppressants.
In view of the dissimilar causes of depression and 20 psychosis, the antipsychotic activity of the present compounds could not have been predicted.
The present invention relates to the use of a compound of the formula: 81047 -2- I z or of a pharmaceutical^ acceptable acid addition salt thereof, wherein is hydrogen or alkyl; R2 is Cx-C3 alkyl; wherein X and Y are each independently selected from the group consisting of hydrogen, fluoro, chloro. bromo, tr i f luoromethy 1 , nlkoxv of from | to 3 carbon atoms and cyano, with at least one of X and Y other than hydrogen; and W is selected from the group consisting of hydrogen, fluoro, chloro, bromo, trifluoromethy1 and alkoxy of from 1 to 3 carbon atoms, for the manufacture of a medicament for the treatnent of psychosis cx inQHnraticn or for use as an immunosuppressant.
The compounds of the formula I include both the cis and the trans isomers. In the cis isomer, the NRj^Rj and Z moieties are both oriented on the same side of the cyclohexane ring. In the trans isomer, the ^1^2 ^ moieties are oriented on opposite sides of the cyclohexane ring. Because both the 1 and 4 carbons of Formula I are asymmetrically substituted, each cis compound and each trans compound has two optically Z is -3- active enantiomeric forms denoted, respectively, cis -(1R) and cis - (IS) and trans - (1R) and trans - (IS). The preponderance of the pharmaceutical activity of the cis-isomer compounds of the formula I resides in the 5 (IS)-enantiomeric forms thereof, while the preponderance of pharmaceutical activity of the trans-isomer compounds of formula I resides in the (IS)-enantiomeric forms.
Preferred compounds or their pharmaceutically 10 acceptable acid addition salts for use in the present invention are: Cis (IS)(4S)-N-methyl-4-(3,4 —dichlorophenyl) -1,2,3,4-tetrahydro-l-naphthalenamine; Cis (IS) (4S)-N-methyl-4-(4-chlorophenyl)-15 1,2,3,4-tetrahydro-l-naphthalenamine; Cis (IS) (4S)-N-methyl-4-(3-trifluoromethy 1-4-chloropheny1) —1,2,3,4-tetrahydro-l-naphthalenamine; Trans(IS)(Mr)-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-l-naphthalenamine; 20 Trans(1R)(4S)-N-methyl-4-(3,4-dichlorophenvl)- 1,2,3,4-tetrahydro-l-naphthalenamine; Cis(1R)(4R)-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-l-naphthalenamine; and Cis (IS) (4S)-N,N-dimethyl-4- (3,4-dichlorophenyl)-25 1,2,3,4-tetrahydro-l-naphthalenamine, The compounds of the formula I or the pharmaceutically acceptable acid addition salts thereof may be prepared and formulated as described in United States Patents 4,556,676 and 4,536,518- The compounds of the formula I or the pharmaceutically acceptable acid addition salts thereof are useful in treating psychotic disorders in mammalian subjects (e.g. humans). More specifically the present compounds are of use in the treatment of schizophrenia, delusional disorder, brief-reactive psychosis, schizo-effective disorder, atypical psychosis, mania and in emotion discontrol in dementia. For example, the compounds salts are useful in treating psychotic disorders of the schizophrenic types, and especially for removing or ameliorating such symptoms and conditions as anxiety, agitation, tension, excessive aggression and social and/or emotional withdrawal, etc. that one normally encounters when dealing with psychotic patients.
The compounds of the formula I or the pharmaceutically acceptable salts thereof are also useful in treating inflammatory disorders in mammals (e.g. humans), including psoriasis, arthritis and inflammatory based diseases.
The compounds of the formula I or the pharmaceutically acceptable salts thereof are also useful as immunosuppressants.
Such compounds are useful in connection with transplant surgery and in treating conditions such as rheumatoid arthritis, lupus, and other autoimmune diseases or diseases characterized by immune hyperfunction.
For use as discussed above, the compounds of formula I or the pharmaceutically acceptable salts thereof may be administered to a subject in need of treatment by a variety of conventional routes of administration, including oral, by injection, topical, and in an aerosol carrier composition for administration by breathing. -5- In general, the compounds of the formula I and the pharmaceutically acceptable salts thereof are most desirably administered in doses ranging from 0.1 mg. up to 100 nig, per day, although variations 5 will necessarily occur depending upon the weight and condition of the subject being treated and the particular route of pharmaceutical administration chosen. However, a dosage level that is in the range of from 0.3 mg to 10 mg per kg of body 10 weight per day is most desirably employed.
Nevertheless, variations may still occur depending upon the species of animal being treated and its individual response to said medicament, as well as on the type of pharmaceutical formulation chosen and the time period 15 and interval at which such administration is carried out. In some instances, dosage levels below the lower limit of the aforesaid range may be more than adequate, while in other cases, still larger doses may be employed without causing harmful side effects provided 20 that such higher dose levels are first divided into several small doses for administration throughout the day.
Although the compounds of formula I can be administered alone, they will generally be administered 25 in admixture with a pharmaceutical carrier selected with regard to the intended route of administration and standard pharmaceutical practice. For example, oral administration may be in the form of tablets containing such excipients as starch or lactose, or in capsules 30 either alone or in admixture with excipients, or in the form of elixirs or suspensions containing flavoring or coloring agents. In the case of animals, they are advantageously contained in an animal feed or drinking t -6- water. For parenteral injection, they may be used in the form of a sterile aqueous solution which may contain other solutes, for example enough salt or glucose to make the solution isotonic with blood. 5 The antipsychotic, antiinflammatory and immunosuppressive activity of the compounds of the formula I and the pharmaceutically acceptable acid addition salts thereof is demonstrated by the following examples. 10 Example 1 In Vitro Binding Affinity of disclosed compounds for sigma receptors in brain tissue was ascertained by the degree of inhibition of binding of the sigma site radioligand, 3 15 ( + )-[ H]3-(3-hydroxypheny1)—N-(1-propyl)piperidine ( (+) - ["^H] 3-PPP) in competition experiments in vitro. These experiments were conducted by the method of Largent et al. Proc. Nat. Acad. Sec. USA, 8_1 4983-87 (1984). Brains were removed from Sprague-Dawley CD 20 male rats (Charles River Breeding Laboratories, Inc., Wilmington, MA; 200-300 g) following decapitation.
Whole brain was homogenized in 25 volumes (v/w) of ice-cold 50 mM Tris (tris(hydroxymethyl)amino methane) hydrochloride pH 7.7 buffer using a Polytron PT-10 25 homogenizer. The pellet resulting from centrifugation of the homogenate at 45,000 x g for 10 minutes at 0-5° was washed twice by resuspension in the same volume of fresh buffer and recentrifugation. The final pellet was dispersed in 50 mM Tris hydrochloride pH 8.0 buffer 30 (50 ml/g of original weight; "tissue preparation"). The incubation mixture in triplicate was comprised of 0.05 ml blank (10 M pentazocine for nonspecific -7- binding), test compound or vehicle; 0.20 ml (+)-[3H]3-PPP (110 Ci/mmol, NENR DuPont; 3 nM final concentration) in 50 mM Tris hydrochloride pH 8.0 buffer; and 0.75 ml tissue preparation. The latter was 5 added just prior to incubation of the mixture at 25°C for 90 minutes. Afterwards, the mixture was diluted with 2.5 ml 10 mM Tris hydrochloride pH 7.7 buffer and filtered under vacuum through a Whatman GF/B glass-fiber filter (pretreated with 1% polyethyleneimine) in 10 a Brandell cell harvester to recover the membranes.
The filter was washed twice with the diluent buffer and placed in 10 ml Aquasol-2 (NEN DuPont Co.) for determination of bound radioactivity in a liquid scintillation counter. Percent inhibition of specific 3 15 (+)-[ H]3-PPP binding was calculated and the concentration inhibiting binding by 50% (IC^q) was determined .
Example 2 In Vivo Binding 20 The efficacy of disclosed compounds for binding to brain sigma receptors in vivo was determined by comparing the labeling of these receptors in intact control and drug-pretreated mice with intravenously 3 administered (+)-[ H]3-PPP. These experiments were 25 conducted by the method of Koe et al. Eur. J.
Pharmacol. 1989, In press. Mice (male Swiss albino from Charles River Breeding Laboratories, Inc., Wilmington, MA; 23-28 g) in groups of 5 received vehicle (controls) and 3 log doses of test compound 30 intraperitioneally 30 minutes before an intravenous injection of (+)-[3H]-PPP (400 Ci/kg). Five minutes later mice were killed by cervical dislocation and whole brains were removed and immediately frozen.
Frozen brains were individually homogenized in -8- 18 ml of ice-cold 50 mM Tris hydrochloride pH 8.0 buffer with a Polytron PT-10 homogenizer. Triplicate 1.0 ml aliquots were filtered under vacuum through Whatman GF/B filters to collect the membranes which 5 were then washed with two 5-ml aliquots of 10 mM Tris hydrochloride pH 7.7 buffer. Membrane-bound radioligand (M) was determined by placing the filters in 10 ml Aquasol-R2 and measuring radioactivity in a liquid scintillation counter. Separate aliquots of the 10 homogenates before filtration were assayed for total radioactivity (H) and protein content. The dose 3 causing 50% inhibition of (+)-[ H]3-PPP binding in vivo (IDj.q) was estimated from semi-log plots of fraction bound (M/H) , calculated as % control, versus dose. -9- TABLE 1 Inhibition of (+)-[3H]3-PPP Binding R r i r 1 i I k 4 , ri V 4 Racemate Substituents on Pendant Phenyl ring IC50 nM (± -trans 4_F nhch3 66 (± -cis 1 n h-» nhch3 33 (± -trans 4-Cl nhch3 75 (± -cis 3,4-diCl nhch3 19 (± -trans 3,4-diCl NHCH3 23 (± -cis 3,4-diCl N(CH3)2 44 (± -trans 3,4-diCl N(CH3)2 30 (± -cis 2,4-diCl NHCH3 29 (± -cis 4-Br NHCH3 13 (± -trans 4-Br NHCH3 85 (± -trans 3-CF3 NHCH3 16 (± -cis 4-cf3 NHCH3 5 (± -trans 4-cf3 NHCH3 39 (± -cis 3-CF3,4-Cl NHCH3 11 (± -trans 3-CF3,4-Cl NHCH3 31 3 nM (+)-[3H]-3-PPP -10- TABLE 2 Of (+)-[3H]3-PP R 4 on Pendant (+)-IS,4S 4-Cl NHCH3 8.7 (+)-IS,4S 3,4-diCl MHCH^ 6.8 (-)-1R,4R 3,4-diCl NHCH3 220 (+)-1R,4S 3,4-diCl NHCH3 51 10 (-)-IS,4 R 3,4-diCl NHCH3 6.6 (+)-IS,4S 3,4-diCl N(CH3)2 28 (+)-IS,4S 3-CF3,4-Cl NHCH, 17 3 nM (+)-[3H]3-PPP -11- TABLE 3 Inhibition of (+)-[3H]3-PPP Binding to Mouse Brain In Vivo Conformation R ^^50 nol/kg i-p• (+ )-1S,4 S NHCH3 0.7 2 (-)-1R,4 R NHCH3 17 (+)-1R,4S NHCH3 3.6 (-)-IS,4 R NHCH3 0.43 400 Ci/kg ( + )-[ 3HI3-PPP i.v.

Claims (2)

1. CLAIMS 1. The use of a compound of the formula: or of a pharmaceutically eplab le acid addition salt thereof, wherein R-L is hydrogen or C^-C^ alkyl; R-, is Cj-C-j alkyl; Z i s wherein X and Y are each independently selected from the group consisting of hydrogen, fluoro, chloro, bromo, trifluoromethyl, alkoxy of from 1 to 3 carbon atoms and cya.no, with at least one of X and Y other than hydrogen; and W is selected from the group consisting of hydrogen, fluoro, chloro, bromo, trifluoromethy1 and alkoxy of from 1 to 3 carbon atoms, for the manufacture of a medicament for the treatment of psychosis.
2. The use of a compound of the formula (I), or of a pharmaceutically acceptable acid addition salt thereof, as defined in claim 1, for the manufacture of a medicament for the treatment of inflammation or for use as an immunosuppressant. 3- Use as claimed in claim 1 for the treatment of schizophrenia, delusional disorder, brief-reactive psychosis,schizo-effective disorder, atypical psychosis, mania and in emotion discontrol in dementia. M. Use according to any preceding claim wherein said compound is the cis or the trans isomer. 5. Use according to claim 4 wherein said compound is Cis (IS) ( 4S)-N-methyl-4-( 3 , 4-dichloropheny 1) -1,2,3,4- tetrahydro-l-naphthalenamine. 6. Use according to claim 4 wherein said compound is Cis( IS) ( 4S)-N-methyl-4-( 4-chlorophenyl) - 1,2, 3,4-tetrahydro-1-naphthalenamine. 7. Use according to claim 4 wherein said compound is Cis(lS)(4S)-N-methyl-4-( 3-t ri f luoromethy 1-4-chlorophenyl)-1,2,3,4-tetrahydro-l-naphthalenanine. 8. Use according to claim 4 wherein said compound is Trans (IS)(4R) -N-methy 1-4-( 3, 4-dichlorophenyl )-l, 2, 3,4-tetrahydro-l-naphthalenauine. 9. Use according to claim 4 wherein said compound is Trans (1R) ( 4S)-N-methyl-4-( 3, 4-dichlorophenyl )-l, 2, 3,4-tetrahydro-l-naphthalenamine. 10. Use according to claim 4 wherein said compound is Cis(1R)(4R)-N-methy1-4-(3,4-dichlorophenyl)-l,2,3,4-tetrahydro-l-naphthalenamine. 11. Use according to claim wherein said compound is Cis( IS) ( 4S)-N,N-dimethyl-1J-( 3, ^-dichlorophenyl)-1,2,3,4-tetrahydro-l-naphthalenamine. 12. Use according to any one of Claims 1, 2 or 3, substantially as hereinbefore described and exemplified. ANNE RYAN & CO. AGENTS FDR THE APPLICANTS
IE79890A 1989-03-07 1990-03-07 Use of 4-phenyl-1,2,3,4-tetrahydro-1-naphthalenamine derivatives in the treatment of phsychosis inflammation stroke and as immunosuppressants IE81047B1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US07/320,014 US4981870A (en) 1989-03-07 1989-03-07 Use of 4-phenyl-1,2,3,4-tetrahydro-1-naphthalenamine derivatives in the treatment of psychosis, inflammation and as immunosuppressants

Publications (2)

Publication Number Publication Date
IE900798L true IE900798L (en) 1990-09-07
IE81047B1 IE81047B1 (en) 1999-12-01

Family

ID=23244506

Family Applications (1)

Application Number Title Priority Date Filing Date
IE79890A IE81047B1 (en) 1989-03-07 1990-03-07 Use of 4-phenyl-1,2,3,4-tetrahydro-1-naphthalenamine derivatives in the treatment of phsychosis inflammation stroke and as immunosuppressants

Country Status (17)

Country Link
US (2) US4981870A (en)
EP (1) EP0386997B1 (en)
JP (2) JPH0714870B2 (en)
KR (1) KR920005810B1 (en)
AT (1) ATE150299T1 (en)
AU (1) AU610036B2 (en)
CA (1) CA2011428C (en)
DE (1) DE69030212T2 (en)
DK (1) DK0386997T3 (en)
HU (1) HU221624B1 (en)
IE (1) IE81047B1 (en)
IL (1) IL93576A (en)
MY (1) MY106272A (en)
NZ (1) NZ232800A (en)
PH (1) PH26542A (en)
PT (1) PT93351B (en)
ZA (1) ZA901743B (en)

Families Citing this family (50)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4981870A (en) * 1989-03-07 1991-01-01 Pfizer Inc. Use of 4-phenyl-1,2,3,4-tetrahydro-1-naphthalenamine derivatives in the treatment of psychosis, inflammation and as immunosuppressants
WO1991009594A1 (en) * 1989-12-28 1991-07-11 Virginia Commonwealth University Sigma receptor ligands and the use thereof
ES2060547B1 (en) * 1992-06-04 1995-06-16 Ferrer Int IMPROVEMENTS IN THE PURPOSE OF THE INVENTION PATENT N / 9201158 THAT REFERS TO "PROCEDURE FOR OBTAINING NEW DERIVATIVES OF 4-BENCILPIPERIDINE".
ZA944513B (en) * 1993-06-23 1996-01-16 Cambridge Neuroscience Inc Sigma receptor ligands
ES2074946B1 (en) * 1993-07-19 1996-06-16 Ferrer Int NEW COMPOUNDS DERIVED FROM 1,2-ETHANODIAMINE-N, N, N ', N'-TETRAS-SUBSTITUTED.
US20030133974A1 (en) * 1997-07-01 2003-07-17 Curatolo William John Encapsulated solution dosage forms of sertraline
WO1999001121A1 (en) 1997-07-01 1999-01-14 Pfizer Inc. Sertraline salts and sustained-release dosage forms of sertraline
US20040208926A1 (en) * 1997-07-01 2004-10-21 Pfizer Inc Solubilized sertraline compositions
CA2395231C (en) 1999-12-23 2006-08-15 Pfizer Products Inc. Hydrogel-driven layered drug dosage form
DE60234057D1 (en) 2001-07-25 2009-11-26 Raptor Pharmaceutical Inc COMPOSITIONS AND METHODS FOR MODULATING TRANSPORT BY THE BLOOD-BRAIN BARRIER
US6988556B2 (en) * 2002-02-19 2006-01-24 Halliburton Energy Services, Inc. Deep set safety valve
US7087785B2 (en) 2002-09-16 2006-08-08 Sepracor Inc. Treatment of CNS disorders with trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-napthalenamine and its formamide
US8134029B2 (en) 2002-09-16 2012-03-13 Sunovion Pharmaceuticals Inc. Treatment of CNS disorders with trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-napthalenamine
EP1545485A2 (en) * 2002-09-16 2005-06-29 Sepracor Inc. Treatment of cns disorders with trans-4- (3,4-dichlorophenyl)-1,2,3,4-tetrahydro-n-methyl-1-napthalenamine
US20040220153A1 (en) * 2002-09-24 2004-11-04 Jost-Price Edward Roydon Methods and reagents for the treatment of diseases and disorders associated with increased levels of proinflammatory cytokines
RU2361862C2 (en) * 2003-12-29 2009-07-20 Сепракор Инк. Pyrrole and pyrazole daao inhibitors
CN103259027A (en) 2005-04-28 2013-08-21 普罗透斯数字保健公司 Pharma-informatics system
CA2614282A1 (en) * 2005-07-06 2007-01-11 Sepracor Inc. Combinations of eszopiclone and trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-n-methyl-1-napthalenamine or trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-napthalenamine, and methods of treatment of menopause and mood, anxiety, and cognitive disorders
AU2006304787A1 (en) 2005-10-21 2007-04-26 Braincells, Inc. Modulation of neurogenesis by PDE inhibition
CA2625210A1 (en) 2005-10-31 2007-05-10 Braincells, Inc. Gaba receptor mediated modulation of neurogenesis
KR101294014B1 (en) 2006-01-06 2013-08-09 선오비온 파마슈티컬스 인코포레이티드 Cycloalkylamines as monoamine reuptake inhibitors
US8053603B2 (en) * 2006-01-06 2011-11-08 Sunovion Pharmaceuticals Inc. Tetralone-based monoamine reuptake inhibitors
US20100216734A1 (en) 2006-03-08 2010-08-26 Braincells, Inc. Modulation of neurogenesis by nootropic agents
PT2816024T (en) * 2006-03-31 2017-10-20 Sunovion Pharmaceuticals Inc Chiral amines
US7678808B2 (en) 2006-05-09 2010-03-16 Braincells, Inc. 5 HT receptor mediated neurogenesis
AU2007249399A1 (en) 2006-05-09 2007-11-22 Braincells, Inc. Neurogenesis by modulating angiotensin
RU2008152404A (en) * 2006-05-31 2010-07-10 Сепракор Инк. (Us) TREATMENT OF PAIN DISORDERS TRANS 4- (3, 4-Dichlorophenyl) -1, 2, 3, 4-TETRAHYDRO-1-NAPHTHALAMINE AND ITS FORMAMIDE
US7884124B2 (en) * 2006-06-30 2011-02-08 Sepracor Inc. Fluoro-substituted inhibitors of D-amino acid oxidase
US7579370B2 (en) * 2006-06-30 2009-08-25 Sepracor Inc. Fused heterocycles
EP2068872A1 (en) 2006-09-08 2009-06-17 Braincells, Inc. Combinations containing a 4-acylaminopyridine derivative
KR20090071598A (en) 2006-09-18 2009-07-01 랩터 파마슈티컬 인코포레이티드 Treatment of liver disorders by administration of receptor-associated protein(rap)-conjugates
US20100184806A1 (en) 2006-09-19 2010-07-22 Braincells, Inc. Modulation of neurogenesis by ppar agents
US20080082066A1 (en) * 2006-10-02 2008-04-03 Weyerhaeuser Co. Crosslinked carboxyalkyl cellulose fibers having non-permanent and temporary crosslinks
FR2909376A1 (en) * 2006-11-30 2008-06-06 Cerep Sa PROCESSES FOR PREPARING DESMETHULSERTRALINE OR ONE OF ITS PHARMACEUTICALLY ACCEPTABLE SALTS
US20090099248A1 (en) * 2007-01-18 2009-04-16 Sepracor Inc. Inhibitors of d-amino acid oxidase
US7902252B2 (en) * 2007-01-18 2011-03-08 Sepracor, Inc. Inhibitors of D-amino acid oxidase
RU2470011C2 (en) 2007-05-31 2012-12-20 Сепракор Инк. Cycloalkylamines, containing phenyl as substituent, as inhibitors of monoamine reuptake
US20100120740A1 (en) * 2008-08-07 2010-05-13 Sepracor Inc. Prodrugs of fused heterocyclic inhibitors of d-amino acid oxidase
WO2010099217A1 (en) 2009-02-25 2010-09-02 Braincells, Inc. Modulation of neurogenesis using d-cycloserine combinations
TWI556839B (en) 2009-05-06 2016-11-11 研究室護膚股份有限公司 Dermal delivery compositions comprising active agent-calcium phosphate particle complexes and methods of using the same
US20110034434A1 (en) * 2009-08-07 2011-02-10 Sepracor Inc. Prodrugs of fused heterocyclic inhibitors of d-amino acid oxidase
US20120077778A1 (en) 2010-09-29 2012-03-29 Andrea Bourdelais Ladder-Frame Polyether Conjugates
EP2919788A4 (en) 2012-11-14 2016-05-25 Univ Johns Hopkins Methods and compositions for treating schizophrenia
EP2968237A4 (en) 2013-03-15 2016-08-31 Univ Johns Hopkins Methods and compositions for improving cognitive function
DK2968220T3 (en) 2013-03-15 2021-06-14 Agenebio Inc PROCEDURES AND COMPOSITIONS FOR IMPROVING COGNITIVE FUNCTION
KR20170003677A (en) * 2014-05-13 2017-01-09 선오비온 파마슈티컬스 인코포레이티드 Methods and compositions of dasotraline for treatment of adhd
CA2948839A1 (en) * 2014-05-13 2015-11-19 Sunovion Pharmaceuticals Inc. Dosage of dasotraline and method for treatment of adhd
WO2016046669A2 (en) * 2014-09-27 2016-03-31 Mohan M Alapati Compositions and methods for the treatment of depression and neurological diseases
BR112017025031B1 (en) 2015-05-22 2023-03-21 Agenebio, Inc LEVETIRACETAM EXTENDED RELEASE PHARMACEUTICAL COMPOSITIONS
FR3071726B1 (en) * 2017-09-29 2020-09-04 Univ Paris Sud TCTP PROTEIN INHIBITORS FOR THE TREATMENT OF PROLIFERATIVE AND INFECTIOUS DISEASES

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1420472A (en) * 1972-09-27 1976-01-07 Pfizer Aminophenyltetralin compounds
JPS59497B2 (en) * 1979-11-01 1984-01-07 フアイザ−・インコ−ポレ−テツド Antidepressant derivative of trans-4-phenyl-1,2,3,4-tetrahydro-1-naphthalenamine
US4536518A (en) * 1979-11-01 1985-08-20 Pfizer Inc. Antidepressant derivatives of cis-4-phenyl-1,2,3,4-tetrahydro-1-naphthalenamine
US4792448A (en) * 1987-06-11 1988-12-20 Pfizer Inc. Generic zero order controlled drug delivery system
US4981870A (en) * 1989-03-07 1991-01-01 Pfizer Inc. Use of 4-phenyl-1,2,3,4-tetrahydro-1-naphthalenamine derivatives in the treatment of psychosis, inflammation and as immunosuppressants

Also Published As

Publication number Publication date
DE69030212T2 (en) 1997-06-26
EP0386997B1 (en) 1997-03-19
ZA901743B (en) 1991-10-30
PH26542A (en) 1992-08-19
MY106272A (en) 1995-04-29
EP0386997A2 (en) 1990-09-12
AU5079690A (en) 1990-09-20
JPH07173056A (en) 1995-07-11
JPH02300121A (en) 1990-12-12
HU901325D0 (en) 1990-05-28
AU610036B2 (en) 1991-05-09
JP3020808B2 (en) 2000-03-15
IL93576A (en) 1995-12-08
US5061728A (en) 1991-10-29
CA2011428C (en) 1994-11-08
DE69030212D1 (en) 1997-04-24
PT93351B (en) 1996-03-29
US4981870A (en) 1991-01-01
NZ232800A (en) 1997-07-27
JPH0714870B2 (en) 1995-02-22
KR900013949A (en) 1990-10-22
ATE150299T1 (en) 1997-04-15
IL93576A0 (en) 1990-11-29
PT93351A (en) 1990-11-07
IE81047B1 (en) 1999-12-01
KR920005810B1 (en) 1992-07-20
HU221624B1 (en) 2002-12-28
HUT59000A (en) 1992-04-28
EP0386997A3 (en) 1992-04-29
DK0386997T3 (en) 1997-04-14
CA2011428A1 (en) 1990-09-07

Similar Documents

Publication Publication Date Title
IE900798L (en) Use of tetrahydronaphthylamines
AU673998B2 (en) Antipyretic and analgesic methods and compositions containing optically pure R(-) ketoprofen
US4824860A (en) Treatment of Parkinsons disease
DE69233462T2 (en) Composition containing tramadol and a non-steroidal anti-inflammatory agent
CA2151724C (en) Antipyretic and analgesic methods and compositions containing optically pure r-ketorolac
Walsh et al. . Animal Models of Alzheimer's Disease: Role of Hippocampal Cholinergic Systems in Working Memory
RU2157685C2 (en) Pharmaceutical composition showing antidepressant activity
EP0647134A1 (en) Methods and compositions for treating depression and other disorders using optically pure (-) sibutramine
US5561151A (en) Antipyretic and analgesic methods of using optically pure R-etodolac
US4619923A (en) Metal protoporphyrins in the control of tryptophan metabolism
CA2139000A1 (en) Methods and compositions for treating depression and other disorders using optically pure(+) sibutramine
Korsgaard et al. The Effect of Tetrahydroisoxazolopyridinol (THIP) in Tardive Dyskinesia: A New β-Aminobutyric Acid Agonist
AU2002352625A1 (en) Use of norepinephrine reuptake inhibitors for the treatment of cognitive failure
WO1993010787A1 (en) Methods and compositions for treating sleep disorders, convulsive seizures, and other disorders using optically pure (+) zopiclone
Mendlewicz et al. A double‐blind comparative study of remoxipride and haloperidol in schizophrenic and schizophreniform disorders
US5652249A (en) Method of treating depression
EP1652532A1 (en) Medicinal composition
MXPA06000077A (en) Compositions containing a serotonin selective reuptake inhibitor and a 5-ht2a receptor antagonist.
Kinoshita et al. Effects of vinconate on spatial learning impairments induced by medial septal lesion in rats
JP4462382B1 (en) Novel inhibitors for D-aspartate oxidase and D-amino acid oxidase
WO2004034996A2 (en) TREATING ALCOHOL AND OR SUBSTANCE ABUSE BY ANTAGONIZING α 2 ADRENERGIC RECEPTORS WITH WEAK DOPAMINE BLOCKING
US20220331275A1 (en) Combination treatments for central nervous system disorders
AU721924B2 (en) Methods and compositions for treating depression and other disorders using optically pure (-) sibutramine
Usdin Frontiers in Neuropsychiatric Research

Legal Events

Date Code Title Description
MM4A Patent lapsed